Association of the miR-146aC>G, miR-196a2C>T, and miR-499A>G polymorphisms with moyamoya disease in the Korean population.

Recent evidence has demonstrated associations between the single nucleotide polymorphism (SNP) rs11614913 in miR-196a2C>T and various pathologies. A main target of miRNA-196a is annexin A1 (lipocortin1, ANXA1), which is associated with increased multiple malignant tumors in brain models of ischemia and reperfusion injury. To determine the effects of miRNA SNPs in moyamoya disease, we recruited 107 patients with moyamoya disease and 240 healthy controls from a Korean study population and determined the genotype of each participant from whole blood samples. We compared the patient and the control genotypes and allele frequencies of rs2910164, rs11614913, and rs3746444 and investigated the association of the three SNPs with age and clinical characteristics, such as cerebral hemorrhage or infarction. rs11614913 in miR-196a2C>T was significantly associated with moyamoya disease. The association of this SNP with adult age and cerebral infarction was statistically significant compared to the control group, but the association with hemorrhagic moyamoya disease was not significant. The CT+CC genotype of miR-196a2 was represented at an increased frequency among patients with moyamoya disease. However, the distribution of miR-146aC>G and miR-499A>G genotypes was not statistically different between participants who were healthy and those with moyamoya disease. Thus, the SNP rs11614913 is significantly associated with moyamoya disease, as well as cerebral infarction and adult age in patients with moyamoya disease. This study demonstrates a higher frequency of the CT+CC genotype of the SNP rs11614913 in miR-196a2C>T, which suggests that miR-196a2 may play a role in the pathogenesis of moyamoya disease.